1990•Cancer CommunicationsOpen access

Potentiation of Doxorubicin Cytotoxicity by (+)-1,2-Bis-(3,5-dioxopiperazin-l-yl) Propane (ICRF-187) in Human Leukemic HL-60 Cells

Elena Monti, Birandra K. Sinha

Abstract

The bisdioxopiperazine propane, ICRF-187, has been reported to potentiate doxorubicin cytotoxicity in certain tumor cell lines; however, the mechanism of this interaction is not known. In order to define the mechanism of this interaction, we examined the effects of ICRF-187 on doxorubicin cytotoxicity, free radical formation, and drug accumulation in human leukemia HL-60 cells. Studies show that ICRF-187 synergistically potentiated doxorubicin cytotoxicity in HL-60 cells. This potentiation of doxorubicin cytotoxicity by ICRF-187 appeared to result from enhanced drug dependent free radical formation without effecting doxorubicin uptake in HL-60 cells.

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Key concepts: Cytotoxicity, Doxorubicin, Long-term potentiation, Chemistry, Pharmacology, Cell culture, Cancer research, Biochemistry